The overall objective of the proposed research is the identification of genes of Rous sarcoma virus (RSV), a representative RNA tumor virus, responsible for the initiation and maintenance of the transformed state. The functions specified by such genes will be analyzed by the use of conditional-lethal mutants. These broad areas of investigation will be approached through three distinct, but related avenues. RSV mutants will be isolated and characterized with regard to their ability to elevate plasminogen activator levels. In vivo studies of plasminogen activator production will shed light on an important enzymatic function produced by a cell when it is transformed. We will study where, when, and how this enzyme is synthesized relative to the manner in which the cell becomes transformed and maintains the transformed state. In vitro studies on the biochemistry of plasminogen activator should lead to an understanding of its structure and function, and will aid in the design of drugs which specifically interact with it and not with other proteases. These studies also will provide more information on the involvement of proteases in biological control systems.